Calcium channels are membrane-spanning, multi-subunit proteins that facilitate the controlled transport (“flux”) of Ca2+ ions into and out of cells. Cells throughout the animal kingdom, and at least some bacterial, fungal and plant cells, possess one or more types of calcium channels. In general, “excitable” cells, such as neurons of the central nervous system, peripheral nerve cells, and muscle cells, including those of skeletal muscles, cardiac muscles, and venous and arterial smooth muscles, possess voltage-dependent calcium channels. In a voltage-dependent calcium channel, the transport of Ca2+ ions into and out of the cells requires a certain minimal level of depolarization (the difference in potential between the inside of the cell bearing the channel and the extracellular environment) with the rate of Ca2+ cell flux dependent on the difference in potential. In “non-excitable” cells, calcium influx is thought to occur predominantly in response to stimuli which cause the release of calcium from intracellular stores. This process, termed store operated calcium influx, is not well understood.
Characterization of a particular type of calcium channel by analysis of whole cells is complicated by the presence of mixed populations of different types of calcium channels in the majority of cells. Although single-channel recording methods can be used to examine individual calcium channels, such analysis does not reveal information related to the molecular structure or biochemical composition of the channel. Furthermore, in this type of analysis, the channel is isolated from other cellular constituents that might be important for the channel's natural functions and pharmacological interactions. To study the calcium channel structure-function relationship, large amounts of pure channel protein are needed. However, acquiring large amounts of pure protein is difficult in view of the complex nature of these multisubunit proteins, the varying concentrations of calcium channel proteins in tissue sources, the presence of mixed populations of calcium channel proteins in tissues, and the modifications of the native protein that can occur during the isolation procedure.